Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease
Acute kidney injury (AKI) is characterized by a sudden decline in kidney function, often due to ischemia-reperfusion or nephrotoxic drugs. A key factor in AKI development is mitochondrial dysfunction, which disrupts energy and oxygen supply, increases ROS generation, and triggers inflammation. Addre...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642500777X |
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| author | Li-Bin Zhou Xuan-Ze Peng Hui-Min Long Jing-Bo Hu Jian-Ting Xu |
| author_facet | Li-Bin Zhou Xuan-Ze Peng Hui-Min Long Jing-Bo Hu Jian-Ting Xu |
| author_sort | Li-Bin Zhou |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is characterized by a sudden decline in kidney function, often due to ischemia-reperfusion or nephrotoxic drugs. A key factor in AKI development is mitochondrial dysfunction, which disrupts energy and oxygen supply, increases ROS generation, and triggers inflammation. Addressing AKI through mitochondrial targeting remains challenging. Melatonin (MLT), a hormone secreted by the pineal gland, shows promise in AKI treatment. To enhance site-specific antioxidative efficacy, triphenylphosphonium-hyaluronic acid (TPP-HA), targeting CD44 receptors and mitochondria, was synthesized and linked to MLT via a cleavable linker, creating TPP-HA-TK-MLT (THTM). THTM improved MLT targeting in renal tubular epithelial cells through CD44 receptors and enhanced mitochondrial distribution via TPP. This effectively suppressed mitochondrial ROS under pathological conditions, ameliorated mitochondrial permeability and swelling, and increased resistance to stimuli such as ischemia-reperfusion injury or nephrotoxic drugs, reducing cell apoptosis. Moreover, THTM significantly reduced the progression of folic acid-induced kidney injury to chronic kidney disease, demonstrating its potential to lower the risk of chronic kidney disease. |
| format | Article |
| id | doaj-art-7e71a782b03b4b47b9703d69febfe022 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-7e71a782b03b4b47b9703d69febfe0222025-08-22T04:57:19ZengElsevierMaterials Today Bio2590-00642025-10-013410220710.1016/j.mtbio.2025.102207Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney diseaseLi-Bin Zhou0Xuan-Ze Peng1Hui-Min Long2Jing-Bo Hu3Jian-Ting Xu4Department of Urology, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, ChinaDepartment of Urology, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, China; Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, ChinaDepartment of Urology, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, ChinaFaculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, China; Corresponding author.Department of Urology, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, China; Corresponding author.Acute kidney injury (AKI) is characterized by a sudden decline in kidney function, often due to ischemia-reperfusion or nephrotoxic drugs. A key factor in AKI development is mitochondrial dysfunction, which disrupts energy and oxygen supply, increases ROS generation, and triggers inflammation. Addressing AKI through mitochondrial targeting remains challenging. Melatonin (MLT), a hormone secreted by the pineal gland, shows promise in AKI treatment. To enhance site-specific antioxidative efficacy, triphenylphosphonium-hyaluronic acid (TPP-HA), targeting CD44 receptors and mitochondria, was synthesized and linked to MLT via a cleavable linker, creating TPP-HA-TK-MLT (THTM). THTM improved MLT targeting in renal tubular epithelial cells through CD44 receptors and enhanced mitochondrial distribution via TPP. This effectively suppressed mitochondrial ROS under pathological conditions, ameliorated mitochondrial permeability and swelling, and increased resistance to stimuli such as ischemia-reperfusion injury or nephrotoxic drugs, reducing cell apoptosis. Moreover, THTM significantly reduced the progression of folic acid-induced kidney injury to chronic kidney disease, demonstrating its potential to lower the risk of chronic kidney disease.http://www.sciencedirect.com/science/article/pii/S259000642500777XAcute kidney injuryRenal tubular epithelial cellsMitochondriaMelatoninIschemia-reperfusionCisplatin |
| spellingShingle | Li-Bin Zhou Xuan-Ze Peng Hui-Min Long Jing-Bo Hu Jian-Ting Xu Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease Materials Today Bio Acute kidney injury Renal tubular epithelial cells Mitochondria Melatonin Ischemia-reperfusion Cisplatin |
| title | Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| title_full | Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| title_fullStr | Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| title_full_unstemmed | Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| title_short | Stepwise targeting hyaluronic acid-based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| title_sort | stepwise targeting hyaluronic acid based polymeric prodrug for acute kidney injury and prevents its progression to chronic kidney disease |
| topic | Acute kidney injury Renal tubular epithelial cells Mitochondria Melatonin Ischemia-reperfusion Cisplatin |
| url | http://www.sciencedirect.com/science/article/pii/S259000642500777X |
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